Peptide receptor radionuclide therapy

Lutetium-177 treatment CT scan

Peptide Receptor Radionuclide Therapy (PRRT) is a molecular therapy used in nuclear medicine to treat specific types of cancer. This treatment involves the use of molecules that are targeted towards specific receptors on the surface of cancer cells, combined with a radioactive substance. The most common application of PRRT is in the treatment of neuroendocrine tumors (NETs), particularly those that express the somatostatin receptor.

Overview

PRRT exploits the mechanism of action of certain peptides, such as somatostatin analogs, which have the ability to bind to receptors on the surface of tumor cells. By attaching a radioactive isotope to these peptides, the therapy delivers targeted radiation to the tumor, minimizing damage to surrounding healthy tissue. The isotopes commonly used in PRRT include Lutetium-177 and Yttrium-90, both of which emit beta radiation that has a therapeutic effect on the tumor cells.

Indications

PRRT is primarily indicated for the treatment of:

• Neuroendocrine tumors (NETs) that are inoperable or metastatic and show an overexpression of somatostatin receptors. These include tumors originating from the pancreas, gastrointestinal tract, and lungs.
• Certain types of pheochromocytoma and paraganglioma that are inoperable or metastatic and have shown responsiveness to somatostatin analogs in imaging studies.

Procedure

The PRRT procedure involves several steps:

1. Patient Evaluation: Patients undergo diagnostic imaging, such as Somatostatin Receptor Scintigraphy (SRS) or Positron Emission Tomography (PET) using Gallium-68 DOTATATE, to confirm the presence of somatostatin receptors on the tumor cells.
2. Radiopharmaceutical Administration: The chosen radiolabeled peptide is administered intravenously. The administration is typically done in an outpatient setting and may require multiple sessions spaced several months apart.
3. Post-Therapy Imaging: Follow-up imaging is performed to assess the response of the tumor to the therapy and to monitor for any potential side effects.

Side Effects

While PRRT is generally well-tolerated, some patients may experience side effects, including:

• Nausea and vomiting
• Fatigue
• Mild hair loss
• Hematological toxicity, such as anemia, leukopenia, or thrombocytopenia
• Renal toxicity, particularly in patients with pre-existing renal conditions

To mitigate the risk of renal toxicity, patients are often given amino acid infusions before and during the administration of the radiopharmaceutical to protect the kidneys.

Efficacy

Studies have shown that PRRT can lead to significant tumor shrinkage, improved quality of life, and extended survival in patients with metastatic or inoperable neuroendocrine tumors. The therapy is most effective in tumors that highly express somatostatin receptors.

Future Directions

Research is ongoing to explore the use of PRRT in combination with other therapies, such as chemotherapy and immunotherapy, to enhance its efficacy. Additionally, the development of new peptides and radioligands may expand the applicability of PRRT to other types of cancer.